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Berberine
Gels · 2021 ·Vol. 7 ·期 1 ·23 · IF 4.702

Fabrication and Evaluation of Silk Sericin-Derived Hydrogel for the Release of the Model Drug Berberine

Chi Yan,Jianwei Liang,Hao Fang,Xizhi Meng,Jiale Chen,Zhi Zhong,Qin Liu,Hongmei Hu,Xiaoning Zhang

Silk sericin (SS) produced byBombyx moriis normally discarded as waste in manufacturing processes, which causes environmental pollution. Therefore, investigating the use of silk sericin has economic and environmental benefits. As a three-dimensional structure, the sericin-derived hydrogel was explored in different applications. However, many developed gelation procedures raise concerns regarding safety, cost, and duration of gelation time. In this work, “thiol-ene” click chemistry was used to quickly and controllably prepare an SS-derived hydrogel to resolve these early concerns. Then, berberine was loaded and used as a model for investigating the drug-release profiles of the prepared hydrogel. The experimental results revealed that this hydrogel is eligible for a long-term release of berberine. Throughout the antibacterial experiments, the released berberine maintained its antibacterial activity. Our work expands the application of SS in biomedical industries in an eco-friendly way. Furthermore, the discussed strategy could provide a reference for the subsequent development of SS-derived materials.Keywords:silk sericin;thiol-ene;hydrogel;drug delivery

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JOURNAL OF MOLECULAR STRUCTURE · 2023 · IF 3.8

Preparation and antibacterial activity of chitosan grafted cyclodextrin hydrogel loaded berberine hydrochloride using dual gelling agent

Hui Yun Zhou,Pei Yan Hao,Shuai Qiang Jiang,Wan Hui Zhang,Li Jun Ren,Hui Jie Zheng,Ya Wei Chen,Jun Liang Chen,Hyun Jin Park

In this paper, cyclodextrin-grafted-chitosan (CD-g-CS) with different degrees of substitution (DS) was synthesized successfully by the reaction of O -p-toluenesulfonyl-β-cyclodextrin (TCD) and chitosan (CS), and a novel injectable thermosensitive hydrogel with rapid gelation was developed by physical cross-linking using dual gelling agents of αβ-glycerophosphate-sodium and hydrogen carbonate (GP-SHC). The results of 1 H-NMR showed that the DS of CD-g-CS increased with the increase of TCD/CS (w/w). The influence of CD-g-CS with different DS, the concentration of SHC, and the ratio of CD-g-CS/GP-SHC (v/v) on gel time, swelling, drug release, degradation, and antibacterial activity of hydrogels prepared were studied. The results of FTIR indicated that the intermolecular interaction occurred in the hydrogel. And the hydrogel had a three-dimensional porous structure seen from SEM images. Compared with CS/GP hydrogel, the gel time of prepared hydrogel was shorter, which was less than 6 min, and the shortest gel time was 0.5 min. The prepared hydrogels had a good swelling ratio and degradable behavior. Berberine hydrochloride (BBH) was used as a model drug, and the gel showed a sustained drug release profile. In addition, the hydrogel had excellent antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) . Therefore the BBH@CD-g-CS/GP-SHC hydrogels had great potential in the development of biomedical drug delivery systems and antibacterial materials.

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Molecular Medicine Reports · 2020 ·Vol. 22 ·期 5 ·4227-4235 · IF 2.1

Berberine protects against diabetic retinopathy by inhibiting cell apoptosis via deactivation of the NF‑κB signaling pathway

Jiajia Zhai,Zeping Li,Huifeng Zhang,Louyan Ma,Zhengquan Ma,Yi Zhang,Jian Zou,Mo Li,Li Ma,Xin Wang,Xiaomiao Li

A number of studies have reported that diabetic retinopathy (DR) is the major cause of blindness. Berberine (BBR) is a bioactive constituent that displays effects on blood glucose; however, the mechanism underlying the role of BBR during the development of DR is not completely understood. In the present study, a rat model of DR was successfully established. The eye tissues were removed and subsequently assessed by hematoxylin and eosin staining and the TUNEL assay. The catalase, malondialdehyde, reactive oxygen species, glutathione and superoxide dismutase contents of the eye tissues were measured. Müller cells were chosen for further in vitro experiments. Cell apoptosis was examined by Annexin V‑FITC apoptosis detection and Hoechst staining, and the mitochondrial membrane potential was assessed by JC‑1 mitochondrial membrane potential detection. BBR decreased ganglion cell layer, cell apoptosis, reduced diabetic‑induced oxidative stress and deactivated the NF‑κB signaling pathway in the rat model of DR. High glucose enhanced oxidative stress and induced mitochondria‑dependent cell apoptosis in Müller cells by activating the NF‑κB signaling pathway. BBR reversed the high glucose‑induced effects by decreasing the phosphorylation of IκB, inhibiting NF‑κB nuclear translocation and deactivating the NF‑κB signaling pathway. The results suggested that BBR protected against DR by inhibiting oxidative stress and cell apoptosis via deactivation of the NF‑κB signaling pathway; therefore, suggesting that BBR may serve as a promising therapeutic agent for DR.

✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Bio Materials · 2026 · IF 5.6

Chitosan-Based Thermosensitive Hydrogel Codelivering Berberine and Resveratrol Promotes Wound Healing of Bacterial Infection in Diabetic Mice

Zhengrong Chen,Jiaxin Yan,Qingshuang Wang,Yutong Wang,Chunshuang Qi,Xue Jiang,Xincui Shi,Xiangru Feng

Diabetic bacterial infected wounds are severe complications in diabetic patients, posing significant challenges to clinical management. The wound site is prone to bacterial colonization and biofilm formation, triggering a persistent inflammatory response and forming a vicious cycle of “hyperglycemia−infection−inflammation”. Therefore, the development of antibacterial materials that are efficient, safe, and less likely to induce drug resistance is of great significance for improving wound repair. In this study, a thermosensitive composite hydrogel based on chitosan (CS) and poloxamer (P407/P188), named CPP, was developed for the codelivery of berberine (BBR) and resveratrol (RES). This system undergoes a phase transition at physiological temperature to form a porous network structure, enabling controllable and sustained drug release. In vivo experiments using a diabetic mouse model with infected wounds showed that the CPP@BBR@RES hydrogel effectively inhibited bacterial colonization, alleviated the inflammatory response, and significantly promoted collagen deposition, angiogenesis, and wound closure. This study innovatively combines the thermogelling and sustained-release properties of the material with the synergistic antibacterial, anti-inflammatory, and repair-promoting functions of the dual drugs, providing a multifunctional integrated therapeutic strategy for diabetic infected wounds.

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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Berberine-Based Heterogeneous Linear Supramolecules Neutralized the Acute Nephrotoxicity of Aristolochic Acid by the Self-Assembly Strategy

Penglong Wang,Wenbo Guo,Guangrui Huang,Jianhua Zhen,Yini Li,Tong Li,Lu Zhao,Kai Yuan,Xuehao Tian,Xuemei Huang,Yanyan Feng,Haimin Lei,Anlong Xu

Aristolochic acid (AA) has been reported to cause a series of health problems, including aristolochic acid nephropathy and liver cancer. However, AA-containing herbs are highly safe in combination with berberine (Ber)-containing herbs in traditional medicine, suggesting the possible neutralizing effect of Ber on the toxicity of AA. In the present study, in vivo systematic toxicological experiments performed in zebrafish and mice showed that the supramolecule self-assembly formed by Ber and AA significantly reduced the toxicity of AA and attenuated AA-induced acute kidney injury. Ber and AA can self-assemble into linear heterogenous supramolecules (A–B) via electrostatic attraction and π–π stacking, with the hydrophobic groups outside and the hydrophilic groups inside during the drug combination practice. This self-assembly strategy may block the toxic site of AA and hinder its metabolism. Meanwhile, A–B linear supramolecules did not disrupt the homeostasis of gut microflora as AA did. RNA-sequence analysis, immunostaining, and western blot of the mice kidney also showed that A–B supramolecules almost abolished the acute nephrotoxicity of AA in the activation of the immune system and tumorigenesis-related pathways.

CAS / MDL: 7440-41-7
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Journal of Analytical Science and Technology · 2021 ·Vol. 12 ·期 1 ·1-9 · IF 2.769

A cationic quantum dot-based ratiometric fluorescent probe to visually detect berberine hydrochloride in human blood serums

Liu Mingyang,Du Xuejun,Xu Ke,Yan Binwei,Fan Zaibi,Gao Zideng,Ren Xueqin

Berberine hydrochloride (BH) is an isoquinoline alkaloid normally used as drug to treat diseases. Compared with the traditional detection methods, the carbon quantum dots (CQDs) have better selectivity, high sensitivity, easy operation, and is inexpensive which could be widely utilized as fluorescent nanoprobes to detect various compounds quantificationally. And ratiometric fluorescent sensors conspicuously increase sensitivity and precision detection and improve quantification. In this work, we use water-soluble and fluorescent cationic carbon dots cetylpyridinium chloride monohydrate (CPC)-CQDs to connect with pinacyanol chloride (PC) and sodium tetraphenylborate (ST) as the ratiometric fluorescent probe to detect BH. The ratiometric fluorescent probe has high sensitivity towards alkaloids and metal ions, photochemical stability (60 min), and pH stability (from 6.0 to 8.0), with the detection range from 0 to 200 μM, and limit was as low as 57.35 nM. The accuracy of the method was verified by spiked recovery experiment in different human blood serums which were drawn from healthy adult volunteers to explore the practicability. The recoveries were in the range 94.34 to 105.48% with relative standard deviations (RSD) of 0.80 to 2.92%. In addition, we could observe that the fluorescence was gradually darkened, and the color turned yellow to realize the visual detection. It is expected that this work would open up a new strategy for detecting BH in the environment and human blood serums.

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PHARMAZIE · 2020 ·Vol. 75 ·期 10 ·483-487 · IF 1.198

Crystal structure, dissolution and hygroscopicity of a novel cocrystal hydrate of berberine hydrochloride with L(+)-lactic acid

Wang Lili,Liu Shuyu,Gao Ziyao

Berberine hydrochloride (BCl) is commercially used to treat diarrhea, diabetes, hyperlipidemia, and cancer. However, BCl suffers from solid state instability, low aqueous solubility, low dissolution rate, and poor bioavailability, which limit its potential application in clinical medicine. In this work, we report a novel cocrystal hydrate of BCl with L(+)-lactic acid (BCl-LA-H2O), designed to improve its physicochemical properties, thus promoting its application in the pharmaceutical industry. As a result, the cocrystal strategy improved the solubility, dissolution, melting point, and hygroscopicity of BCl, which indicated that the BCl-LA-H2O can be used as a better solid form.

CAS / MDL: 79-33-4
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ACS Omega · 2021 · IF 3.512

Temperature and pH Dual Responsive Nanogels of Modified Sodium Alginate and NIPAM for Berberine Loading and Release

Shuhua Chang,Dawei Qin,Rongjun Yan,Mengli Zhang,Binglin Sui,Hui Xu,Zhaomin Zheng,Xiaoli Hou,Yonggang Wang,Chenggang Qi

pH- and temperature-sensitive nanogels (NGs) were prepared from sodium alginate (SA) and N-isopropylacrylamide (NIPAM), as the sensitivity at pH 5.5 and 31 °C. SA was pH-modified with glutamic acid (Glu) and ethylenediamine (EDA). The products Glu-SA (Glu-modified SA) and EGSA (EDA- and Glu-modified SA) were characterized by ninhydrin color reaction, infrared spectroscopy, and zeta potential, and the best reactant ratio was selected. Moreover, temperature-sensitive, pH-sensitive EGSA-NGs possessing a semi-interpenetrating network structure were prepared by radical polymerization using N-isopropylacrylamide. The morphology of EGSA-NGs was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The cytotoxicity test shows the low cytotoxicity and high biocompatibility of the NGs. The newly prepared NGs were also subjected to pH-sensitive temperature-sensitive in vitro drug-loading and drug-release experiments. The pH-sensitive and temperature-sensitive experiments showed that the particle size of EGSA-NGs was reduced at pH 5.5 and above 31 °C. The drug-loading and drug-release experiments also confirmed this finding, indicating that the newly synthesized NGs could release the drug according to the environmental changes. Therefore, the material has potential application value in solid tumor targeted therapy.

CAS / MDL: 6461-04-7
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LIFE SCIENCES · 2019 · IF 3.448

MDM2 inhibition-mediated autophagy contributes to the pro-apoptotic effect of berberine in p53-null leukemic cells

Jian Liu,Zhenjing Zhu,Yueyao Liu,Linlin Wei,Bai Li,Fengxia Mao,Ju Zhang,Yingchao Wang,Yufeng Liu

Aims Berberine (BBR) is reported to induce apoptosis and inhibit migration of leukemic cells, but the underlying pharmacological mechanisms have not been fully revealed. This study aims to investigate the possible mechanisms from the perspective of autophagy. Main methods P-53-null leukemic cell lines Jurkat and U937 were used for the in vitro study. MDC staining was used for observation of autophagy in leukemic cells, and Western blot analysis was for determination of the expression levels of autophagy-associated proteins. Apoptosis of the leukemic cells was detected by flow cytometry. Cellular location of MDM2 was observed with immunofluorescence staining. Ubiquitination of MDM2 was assessed by immunoprecipitation. Male 6–8-week-old NOD/SCID mice were used for evaluating the effect of BBR on chemotherapy sensitivity in vivo . Key findings BBR induced autophagy in p53-null leukemic cells, which was inhibited by autophagy inhibitors 3-methyladenine. 3-methyladenine also inhibited BBR-induced apoptosis in leukemic cells. In addition, BBR not only decreased MDM2 mRNA expression, but also enhanced MDM2 self-ubiquitination in leukemic cells. Forced overexpression of MDM2 reversed the effect of BBR on autophagy and apoptosis. Furthermore, BBR promoted doxorubicin-induced autophagy and cell death in the leukemic cells and overexpression of MDM2 suppressed these effects. In vivo , BBR combined with doxorubicin achieved better therapeutic effect than doxorubicin alone. Significance MDM2 inhibits autophagy and apoptosis in leukemic cells in a p53-independent manner. BBR induces autophagy in p53-null leukemic cells through downregulating MDM2 expression at both transcriptional and post-transcriptional levels, which may contribute to the anti-cancer effect of BBR in leukemia.

CAS / MDL: 633-65-8
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2019 · IF 2.606

Berberine-loaded solid proliposomes prepared using solution enhanced dispersion by supercritical CO2: Sustained release and bioavailability enhancement

Jingfu Jia,Kerong Zhang,Xue Zhou,Jinfang Ma,Xiaojing Liu,Anya Xiang,Fahuan Ge

In present study, berberine proliposomes (ber-PL) of powder state that can form liposomal structure via self-assemble in water was prepared using solution enhanced dispersion by supercritical CO 2 (SEDS) to improve the oral bioavailability of berberine. Several important parameters were optimized using Box-Behnken design to get ber-PL with high entrapment efficacy ( EE ) of 90.3% ± 4.9%. Physicochemical characterization showed the optimum ber-PL was amorphous spherical nanoparticles and could form uniform liposomes around 80 nm easily via hydration. EE was closely related to the particle morphology of ber-PL. In vitro drug release study displayed a sustained release profile, and the drug released faster in neutral condition than acid medium. The oral bioavailability for ber-PL was 22.47 times greater than raw berberine, and the mean residence time of berberine in plasma was extended from 6.82 ± 2.99 to 10.83 ± 2.01 h as well. The proliposome formulated using SEDS is a favorable strategy to improve the bioavailability of berberine.

CAS / MDL: 57-88-5 633-65-8
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY · 2018 · IF 3.165

Ameliorative effect of berberine coated bio-active nanoparticles in acetaminophen induced hepato-renal damage in diabetic rats

Yueyue Wu,Xinmei Huang,Min Yang,Jiong Xu,Zaoping Chen,Zhiyan Yu,Jun Liu

The current investigation was performed for the detailed analysis of protective effect of biofabricate berberine coated nano‑silver ameliorate (BBR-AgNPs) on acetaminophen (APAP) induced hepato-renal damages in diabetic rats by blood biochemistry , tissue biochemistry , histopathological and immunohistochemical analysis. The spherical shaped BBR-AgNPs were synthesized by the Biofabrication technique and its physico-chemical characterizations done by different spectroscopic (UV–vis spectrophotometer , XRD spectroscopy, FTIR spectroscopy EDAX & DLS analyses) and microscopic (FE-SEM) techniques. The diabetic developed rats were administrated with APAP (2.0 g/5 mL/kg) and scrutinize its hepato-renal injuries. The synthesized BBR-AgNPs (75 mg/kg p.o) was administrated orally to the APAP-induced diabetic rats. The result of biochemical markers and lipid peroxidation were significantly (P ˂ 0.05) increased in APAP-induced diabetic rats but decreased the level of antioxidants (P ˂ 0.05), which results obtained in liver and kidney compared to the control group. Immunohistochemical studies result showed that the APAP-induced diabetic rats expressed a high immunoreactivity of nuclear transcription factor (NF-kB). Whereas, the acetaminophen-induced diabetic rats were treated with BBR-AgNPs renovated the changes in the above parameters analyzed. The results of the study clearly indicated that the BBR-AgNPs possess the antioxidant properties as well as anti-diabetic effects, furthermore, the acetaminophen-induced liver and kidney damage was probably inhibited by the inhibition of proinflammatory factor & NF-kB factors.

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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2018 · IF 2.88

Highly selective fluorescent visual detection of perfluorooctane sulfonate via blue fluorescent carbon dots and berberine chloride hydrate

Zhen Cheng,Hongcen Dong,Jiaman Liang,Fang Zhang,Xianping Chen,Lingling Du,Kejun Tan

As a kind of emerging persistent organic pollutants , perfluorooctane sulfonate (PFOS) and its salts have caused global ecosystem pollution. To develop rapid, sensitive and low-cost detection method of PFOS is of great importance. In this work, a novel sensing method has been proposed for the highly selective fluorescent visual detection of PFOS in aqueous solution based on carbon dots (CDs) and berberine chloride hydrate (BH). It was found that the fluorescence of CDs decreased apparently in the presence of berberine chloride hydrate in pH 6.09 Britton–Robinson (BR) buffer solution. When PFOS was added to the system, the fluorescence was restored slightly at 448 nm and enhanced apparently at 533 nm, but no phenomenon occurred with other perfluorinated compounds . As a consequence, an obviously distinguishable fluorescence color variation (from blue to light yellow) of solution was observed. Under the optimized experimental conditions, the enhanced fluorescence intensities at 533 nm are in proportion to the concentration of PFOS in the range of 0.22–50.0 μmol/L (R 2  = 0.9919), with a detection limit of 21.7 nmol/L (3σ). The proposed approach has been successfully applied to the detection of PFOS in environmental water samples with RSD ≤ 1.1%.

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